本文選題：可溶性CD14　切入點：Toll樣受體4　出處：《第一軍醫(yī)大學》2006年博士論文　論文類型：學位論文

【摘要】：在移植免疫中，T淋巴細胞在雙信號刺激下才能被激活和發(fā)生增殖，從而啟動由淋巴細胞、細胞因子、補體等參予的錯綜復雜的移植排斥反應。如果抗原提呈細胞(antigen present cell，APC)只提供MHC-抗原肽復合物而不提供CD80、CD86等共刺激信號，將使淋巴細胞無能，誘導免疫耐受。 目前，國內(nèi)、外關(guān)于移植免疫的研究主要集中在以T／B淋巴細胞及其下游細胞因子為中心的免疫過程，由于T／B淋巴細胞活化后移植免疫網(wǎng)絡的復雜性，以該免疫網(wǎng)絡某一個環(huán)節(jié)為靶點的治療措施往往事倍功半。 顯然，針對淋巴細胞活化的上游信號傳導者APC的研究將具有顯而易見的優(yōu)勢。APC表面共刺激分子的表達是決定T細胞異基因免疫反應性的關(guān)鍵因素。APC表面CD80、CD86等共刺激分子的下調(diào)可以使APC轉(zhuǎn)變?yōu)橹履褪苄约毎筎細胞失去發(fā)生異基因反應的能力。 但問題是，CD80、CD86的表達是由誰調(diào)控的?如何調(diào)控的?1997年，人類天然免疫模式識別受體TOLL樣受體(Toll like receptor，TLR)的發(fā)現(xiàn)使得以APC為主要對象的移植免疫研究成為可能。早期關(guān)于TLR的研究主要集中在抗感染免疫方面，TLR是天然免疫用以識別各種致病微生物共有結(jié)構(gòu)的“工具”，TLR與各種致病微生物共有的保守結(jié)構(gòu)也即病原相關(guān)分子模式結(jié)合后，激活相應的信號傳導通路，促進單核／巨噬細胞、樹突狀細胞等抗原提呈細胞的成熟與活化，上調(diào)CD80、CD86等共刺激分子的表達，啟動天然免疫，消滅入侵的病原體。隨著研究的進一步深入，發(fā)現(xiàn)TLR還在移植免疫、動脈粥樣硬化形成中起重要作用。其中，TLR4與移植免疫關(guān)系的研究顯示出極具誘人的前景。 在可溶性CD14(soluble CD14，sCD14)幫助下，APC上的TLR4與革蘭氏陰性菌內(nèi)毒素脂多糖LPS結(jié)合并活化，通過一系列信號傳導，，引起NF-κB活化，
[Abstract]:In transplant immunity, T lymphocytes can only be activated and proliferated under the stimulation of double signals, and thus activated by lymphocytes, cytokines, If antigen presenting cell antigen present cell (APC) provides only MHC-antigen peptide complex but not costimulatory signal such as CD80 or CD86, it will cause lymphocyte anergy and induce immune tolerance. At present, domestic and foreign researches on transplantation immunity mainly focus on the immune process centered on T / B lymphocytes and their downstream cytokines. Because of the complexity of the transplantation immune network after T / B lymphocytes are activated, Therapeutic measures targeted at one link of the immune network are often half-effective. Obviously, The study on upstream signal transducers of lymphocyte activation will have obvious advantages. The expression of costimulatory molecules on APC surface is the key factor to determine the allogeneic immunoreactivity of T cells. CD80 CD86 and other costimulatory molecules on the surface of APC are the key factors to determine the allogenic immunoreactivity of T cells. The down-regulation of APC can transform APC into tolerant cells. Make T cells lose the ability to produce allogenic reactions. But the question is, who regulates the expression of CD80? How? 1997, The discovery of human innate immune pattern recognition receptor TOLL-like receptor Toll like receptor makes it possible to study transplantation immunity with APC as the main object. Early studies on TLR mainly focused on anti-infection immunity. In order to identify the common structures of various pathogenic microorganisms, the TLR binds to the conserved structure shared by various pathogenic microorganisms, that is, pathogen-related molecular patterns. Activating the corresponding signal transduction pathway, promoting the maturation and activation of antigen-presenting cells such as monocytes / macrophages and dendritic cells, upregulating the expression of costimulatory molecules such as CD80, CD86, and initiating innate immunity. With the further development of research, it is found that TLR still plays an important role in the pathogenesis of atherosclerosis, and the relationship between TLR4 and transplantation immunity is very attractive. Under the help of soluble CD14(soluble CD14s CD14, TLR4 on APC binds and activates lipopolysaccharide (LPS) from gram-negative bacteria, which activates NF- 魏 B through a series of signal transduction.
【學位授予單位】：第一軍醫(yī)大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R699.2;R392.4

【參考文獻】

相關(guān)期刊論文 前2條

1 李曉北,管德林,韓志友,和不朗,韓修武,張衛(wèi)峰,高居忠;彩色多普勒超聲診斷早期移植腎急性排斥[J];中華泌尿外科雜志;2001年12期

2 江海燕,劉艷君,朱平,韓強濤,富寧;人可溶性CD14檢測體系的建立[J];中國實驗診斷學;2004年01期

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